The gastroenterological tract refers to organs playing roles of food ingestion, transport, digestion, absorption of nutrients, and excretion. In the gastroenterological tract, the pancreas is an organ approximately 15 cm long and located behind the stomach. The major diseases are pancreatic cancer and pancreatitis. Particularly, pancreatic cancer is known as one of cancers whose mortality rate among Japanese is increasing. The cause of the pancreatic cancer has not been revealed completely, but the risk factors are presumably excessive intakes of animal fats, proteins, alcohols, and so forth due to Westernization of dietary habits, or smoking and others. In addition, those who have a medical history of chronic pancreatitis, pancreatolithiasis, diabetes, or acute pancreatitis are also thought be in a high risk group of pancreatic cancer. Pancreatic cancer is a cancer developed from a cell having an exocrine function, particularly a cell of the pancreatic duct through which pancreatic juices flow. This type of cancer accounts for 90% or more of pancreatic cancer. Pancreatic cancer has very high malignancy, and metastasizes to another organ at an early stage. Accordingly, early detection is one of the challenges. However, the pancreas exists in the retroperitoneal space and is surrounded by many organs such as the stomach, duodenum, spleen, small intestine, large intestine, liver, and gallbladder. For this reason, it is quite difficult to detect a cancer at the initial stage even by using various kinds of image diagnoses. At present, the cancer is often detected in an advanced state.
Stomach cancer occurs frequently in Japan and Southeast Asia. In the world, the mortality rate of stomach cancer is the second highest among cancers. The prognosis of stomach cancer has been improved by the advancement of diagnostic techniques and treatment methods, but it cannot be said that the prognosis of advanced stomach cancer is favorable yet. As the indicator of the prognosis of stomach cancer having invaded stomach serosa, the five-year survival rate is as low as 35%. One of the main causes of the recurrence after curative resection of advanced cancer is peritoneal metastasis. The therapeutic effects on peritoneal metastasis recurrence by the advancement of chemotherapy have also been observed, but the five-year survival rate is still low. Many steps and many genes are known to be involved in the mechanism of the peritoneal metastasis of stomach cancer. It has been reported that an adhesion molecule-related gene, an apoptosis-related gene, and other genes are deeply involved in the peritoneal metastasis of stomach cancer. Further researches are necessary to reveal the mechanisms of the metastasis of stomach cancer including the peritoneal metastasis of stomach cancer.
Esophageal cancer develops in middle thoracic esophagus in approximately half of cases. In Japan, squamous epithelial cancer accounts for 90% or more of esophageal cancer. Both of the morbidity rate and the mortality rate of men are 5 times or more higher than those of women. It has been previously reported that drinking alcohol and smoking are involved in the carcinogenesis of esophageal cancer. Recently, the involvement of ALDH2 has been reported. A surgery on esophageal cancer is a highly invasive procedure, and esophageal cancer is a disease with an unfavorable prognosis. Recently, with increased incidences of early-stage cancer, there is also increased the number of cases that can be cured completely by an endoscopic therapy. Furthermore, chemoradiotherapy has also demonstrated the effects, and the improvement in therapeutic outcome has been observed. Nevertheless, the prognosis of unresectable advanced cancers is still unfavorable. It is desired to establish a new screening system for early-stage cancer detection and make an advancement of chemotherapy in the future.
One of the cancer-detecting and diagnosing methods having been developed so far is measurement of a tumor marker. Blood tumor markers for diagnosing pancreatic cancer have been already developed such for example as CA19-9 (NPL 1), Dupan-2 (NPL 2), CA-50 (NPL 3), and Span-1 (NPL 4). In addition, several patent publications disclose methods for detecting and diagnosing pancreatic cancer by using a marker of a gene specifically expressed in a tumor cell. Up to now, PANCIA and PANCIB (PTL 1) as well as KCCR13L (PTL 2) have been disclosed as marker genes for pancreatic cancer. Moreover, since a DNA is amplified or deleted at a specific site of a chromosome of pancreatic cancer cells, there is also proposed a method for diagnosing pancreatic cancer by detecting an amplification or deletion at a chromosome site specific to pancreatic cancer.
Further, tumor marker measurement for stomach cancer is characterized by using as a marker a variation in an amount of an already-known non-triple-helical C-terminal telopeptide of type I collagen (ICTP) expressed. There are proposed an appropriate diagnosing marker for advanced stomach cancer, particularly scirrhus stomach cancer (see PTL 3), and a method including: counting the number of demethylated DNAs present in a repeated DNA sequence obtained from a cancerous or non-cancerous tissue specimen; and judging, based on the percentage of demethylated DNAs, whether a prognosis of various cancer diseases such as stomach cancer is favorable or not (see for example, PTL 4).
Further, as to metastatic colorectal cancer, or primary/metastatic stomach cancer or esophageal cancer, there is proposed a screening method using an expression of SI, CDX1, or CDX2 as an index (see PTL 5).
However, a tumor marker is used to grasp the kinetics of an advanced malignant tumor at present. No method for detecting and diagnosing a cancer by utilizing a tumor marker, which is adoptable for early diagnosis has been established yet. Particularly, it is difficult to diagnose pancreatic cancer at an early stage, and the therapeutic outcome is not favorable. A met hod applicable to screening has to be developed as soon as possible.